Ratio of Thyroxine to Thyroxine-Binding Globulin

Abstract

SUMMARYThe thyroxine :thyroxine-binding globulin ratio in serum (T4 :TBG) has been proposed as a measure of thyroid status unaffected by altered binding protein levels. Here 320 apparently euthyroid patients are used to derive euthyroid ranges for serum thyroxine concentrations at specific TBG levels. These ranges are compared with those predicted by a T4 :TBG reference range derived from the same patient data. The comparison suggests that the ratio would give false positives for hyperthyroidism at low TBG levels and false negatives at high TBG levels. To overcome this the use of graphical reporting of results or the relation of patient results to empirical reference ranges appropriate to the TBG level is suggested.Burr et al. 1 suggested the use of the serum concentration ratio of thyroxine to thyroxine-binding globulin (T4:TBG). They found this superior to the free thyroxine index in correcting for abnormal binding protein levels when assessing thyroid status.! On the basis of a mathematical model, however, Roosdorp and Joustra" predicted that euthyroid ranges for T4:TBG would vary with TBG level, while Lecureuil et al. 4 found T4:TBG to be inaccurate when THG concentrations were high or low. In the present paper, the validity of the T4:TBG reference range is assessed using patients' samples. 'Apparently euthyroid' ranges for T4 concentration are derived at each of a range of TBG levels. The same data are used to derive a single 1'4 :TBG reference range, and the disagreement between the two sets of reference ranges is assessed. Patients and methodsThe study included all the thyroid function requests received in this laboratory over a four-week period.These comprised 679 patients, 21 % of whom were inpatients, 43 % outpatients, and 36 % referred by general practitioners.Serum samples were analysed for 1'4 by radio- immunoassay," TBG by radial immunodiffusion" and thyrotrophin (TSH). TSH was determined by a double antibody radioimmunoassay using MRC 68/38 as working standard. Antibody (M168 3578) and TSH for labelling were obtained from the Women's Hospital, Birmingham. Three hundred and forty 'apparently euthyroid' individuals were selected from the sample by excluding all patients previously diagnosed as hyperthyroid or hypothyroid, all those treated for either condition, and all those with TSH concentration greater than 5 mUll. Samples from 40 pregnant women with no evidence of thyroid dysfunction were also analysed to give more results in the upper range of TBG levels. ResultsThe distribution of TBG levels in the apparently euthyroid group is shown in Figure 1. The mean TBG level for this group was 12·14 mg/I ± 2·24 (SD), and for all 679 patients 12·31 mgll ± 2·30 (SD).The patients were grouped on the basis of THG level, and the mean and SD for T4 were calculated for each 1 mg/I increment in TBG between 8 and 17 rngjl, Mean and SD were also calculated for the group of pregnant women with THG in the range 20-24'9 rng/I and for the group with TBG above 25 mg/I, All means and SD were recalculated after excludi...

High serum thyroxine-binding globulin—an important cause of hyperthyroxinaemia

“…The T4/TBG ratio is undoubtedly useful as an index of thyroid function. We have refrained from using it in our patients because the normality of this index is related to the absolute level of serum TBG (Cusick, 1981). Few patients are available with high TBG levels from whom to construct reference ranges.…”